Recent biochemical studies have shown that the liver produces inactive and active forms of coagulation factors II, VII, IX, and X. These particular factors are dependent upon vitamin K for their synthesis. In the proposed research, the conversion of preprothrombin to prothrombin (coagulation factor II) and prothrombin to thrombin will be studied by employing both immunological and coagulation techniques. By the use of the recently developed radioimmunoassay for factor II antigen, this investigation will study the factors which affect II antigen and factor II activity. It is known that animals rendered vitamin K deficient develop a coagulopathy when treated with vitamin E. It is proposed that a similar effect may be seen in humans. In addition, developmental aspects of prothrombin and preprothrombin production have not been evaluated in the human neonate. By using the ratio of factor II antigen to factor II activity in an animal model and in humans with thrombotic disease and human neonates, the biological and physiological significance of finding changes in these ratios may be elucidated. If the vitamin E is affecting vitamin K utilization then one would expect that the ratio of antigen to coagulant activity would increase. The known decrease in factor II activity which normally accompanies the newborn period, and particularly the premature child, could be due to either under-production by the liver or an impaired utilization of vitamin K. In those instances in which there is impaired production, then the data would probably indicate a decrease in both precursor and coagulant activity. However, if due to an inability to utilize vitamin K, then the ratio may increase. In addition, by employing these techniques, newer methods may be developed to investigate other humans with known hypercoagulable states.